Analysis of RUVBL2 expression in malignant melanoma and its correlation with prognosis and immune infiltration.

Abstract

Cutaneous melanoma (SKCM) is a highly aggressive malignant tumor of the skin, characterized by rapid progression, strong metastatic potential, and poor clinical prognosis, which poses a serious threat to human health and imposes a heavy burden on global healthcare systems. Despite significant advances in therapeutic strategies such as targeted therapy and immunotherapy in recent years, the clinical outcomes of SKCM patients remain suboptimal, highlighting the urgent need to identify novel molecular biomarkers and therapeutic targets that can facilitate early diagnosis, accurate prognosis evaluation, and effective treatment of this disease. RUVBL2, a member of the AAA+ ATPase family, has been increasingly recognized as a key regulator in tumorigenesis and progression. Accumulating evidence from previous studies has demonstrated that RUVBL2 exerts oncogenic effects in multiple human malignancies. For instance, knockdown of RUVBL2 can inhibit cell proliferation, promote apoptosis, induce senescence, and suppress migration in hepatocellular carcinoma, and its high expression is closely associated with poor prognosis and chemoresistance. In colorectal cancer, RUVBL2 mRNA modified by m6A can be recognized and bound by YTHDF1 to enhance translation initiation and protein expression, and depletion of RUVBL2 impairs YTHDF1-driven oncogenic translation, leading to cell cycle arrest and apoptosis. Additionally, RUVBL2 has been shown to participate in the regulation of oncogenic signaling pathways, immune evasion, and therapeutic sensitivity in pancreatic cancer, bladder cancer, and breast cancer. However, the expression pattern of RUVBL2 in SKCM, its correlation with clinical prognosis and tumor immune microenvironment, as well as its potential functional role in SKCM progression, have not been fully elucidated to date. In view of the critical role of immune cell infiltration in the pathogenesis and progression of SKCM, and the clinical significance of immune checkpoint inhibitors (e.g., anti-PD-1 and anti-CTLA-4 agents) in SKCM treatment, exploring the association between RUVBL2 and tumor immune infiltration, as well as its predictive value for immunotherapeutic efficacy, is of great importance. Therefore, the present study aims to systematically investigate the expression level of RUVBL2 in SKCM and its correlation with clinical prognosis by integrating public database resources (TCGA, GTEx, and HPA) and in vitro experimental validation. Furthermore, we intend to explore the functional role of RUVBL2 in regulating SKCM cell proliferation, migration, invasion, and apoptosis, and clarify its association with immune cell infiltration and sensitivity to immunotherapy. The findings of this study are expected to provide a theoretical basis for the development of novel diagnostic markers and therapeutic strategies for SKCM.